X-149715882-C-G

Position:

chrX-149715882-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000355220.6(MAGEA11):c.396C>G(p.Asp132Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,209,499 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., 8 hem., cov: 22)

Exomes 𝑓: 0.000011 ( 0 hom. 7 hem. )

Consequence

MAGEA11
ENST00000355220.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.23

Variant links:

Genes affected

MAGEA11 (HGNC:6798): (MAGE family member A11) This gene is a member of the MAGEA gene family. The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEA genes are clustered at chromosomal location Xq28. They have been implicated in some hereditary disorders, such as dyskeratosis congenita. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MAGEA11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.032740653).

BS2

High Hemizygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGEA11	NM_005366.5 linkuse as main transcript	c.396C>G	p.Asp132Glu	missense_variant	5/5	ENST00000355220.6	NP_005357.2
MAGEA11	NM_001011544.2 linkuse as main transcript	c.309C>G	p.Asp103Glu	missense_variant	5/5		NP_001011544.1
MAGEA11	XM_047442106.1 linkuse as main transcript	c.396C>G	p.Asp132Glu	missense_variant	8/8		XP_047298062.1
MAGEA11	XM_011531164.3 linkuse as main transcript	c.372C>G	p.Asp124Glu	missense_variant	4/4		XP_011529466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEA11	ENST00000355220.6 linkuse as main transcript	c.396C>G	p.Asp132Glu	missense_variant	5/5	1	NM_005366.5	ENSP00000347358	P2	P43364-1
MAGEA11	ENST00000333104.8 linkuse as main transcript	c.309C>G	p.Asp103Glu	missense_variant	4/4	5		ENSP00000328177	A2
MAGEA11	ENST00000412632.6 linkuse as main transcript	c.309C>G	p.Asp103Glu	missense_variant	5/5	2		ENSP00000391496
MAGEA11	ENST00000518694.1 linkuse as main transcript	n.1986C>G		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes

AF:

0.000242

AC:

AN:

111429

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

AN XY:

33629

show subpopulations

Gnomad AFR

AF:

0.000851

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000951

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000328

AC:

AN:

182740

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

67336

show subpopulations

Gnomad AFR exome

AF:

0.000382

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1098070

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

363432

show subpopulations

Gnomad4 AFR exome

AF:

0.000417

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000242

AC:

AN:

111429

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

AN XY:

33629

show subpopulations

Gnomad4 AFR

AF:

0.000851

Gnomad4 AMR

AF:

0.0000951

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000215

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2024

The c.396C>G (p.D132E) alteration is located in exon 5 (coding exon 4) of the MAGEA11 gene. This alteration results from a C to G substitution at nucleotide position 396, causing the aspartic acid (D) at amino acid position 132 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.32

DANN

Benign

0.29

DEOGEN2

Benign

0.0028

.;T;T

FATHMM_MKL

Benign

0.0081

LIST_S2

Benign

0.084

T;T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.033

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.63

.;.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.17

N;N;N

REVEL

Benign

0.0060

Sift

Benign

0.76

T;T;T

Sift4G

Benign

0.88

T;T;T

Polyphen

0.0, 0.0020

.;B;B

Vest4

0.059, 0.061

MutPred

0.22

.;.;Loss of helix (P = 0.1706);

MVP

0.35

MPC

0.23

ClinPred

0.0043

GERP RS

-1.3

Varity_R

0.15

gMVP

0.051

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over